Risk-Adapted Strategy Combining Magnetic Resonance Imaging and Prostate-Specific Antigen Density to Individualize Biopsy Decision in Patients With PI-RADS 3 ``Gray Zone'' Lesions

Recent guidelines suggest that biopsy may be omitted in some groups of patients with PI-RADS 3 lesions on mpMRI. In this study, we aimed to evaluate biopsy strategies involving prostate-specific antigen density (PSAd) to avoid unnecessary biopsy versus the risk of missing clinically significant prostate cancer (csPCa) in patients with PI-RADS 3 lesions. Data of 616 consecutive patients who underwent PSAd and mpMRI before prostate biopsy between January 2017 and January 2022 at a single center were retrospectively assessed. All of these patients underwent combined cognitive or fusion targeted biopsy of suspicious lesions and transrectal ultrasonography guided systematic biopsy. PI-RADS 3 based strategies with PSAd and mpMRI combination were created. For each strategy, avoided unnecessary biopsy, reduced ISUP Grade 1, and missed ISUP Grade ≥ 2 ratios were determined. Decision curve analysis (DCA) was used to statistically compare the net benefit of each strategy. DCA revealed that patients who had PI-RADS 3 lesions with PSAd ≥ 0.2, and/or patients who had PI-RADS 4 and 5 lesions had the most benefit, under the threshold probability level between 10% and 50%, which avoided 48.2% unnecessary prostate biopsies and reduced 51% of ISUP grade 1 cases, while missed 17.5% of ISUP grade ≥ 2 cases. (22.1% for ISUP grade 2 and 8.8% for ISUP grade ≥ 3). Strategy 1 (PI-RADS 4-5 and/or PSAd ≥ 0.2), 3 (PI-RADS 4-5 and/or PI-RADS 3 if PSAd ≥ 0.15), and 7 (PI-RADS 4-5 and/or PI-RADS 3 if PSAd ≥ 0.15 and/or PI-RADS 2 if PSAd ≥ 0.2) were the next three best strategies. mpMRI combined with PSAd strategies reduced biopsy attempts in PI-RADS 3 lesions. Using these strategies, the advantage of avoiding biopsy and the risk of missing the diagnosis of csPCa can be discussed with the patient, and the biopsy decision can be made afterwards. Although most studies focus on preventing unnecessary prostate biopsy, patients may not accept the rates of missing clinically significant prostate cancer and the associated clinical risks. Therefore, our risk-adapted strategies allow each patient and clinician to choose the most appropriate strategy for themselves.